Caroline B Appleyard

Ponce Health Sciences University - Ponce Research Institute

Inflammatory Bowel Disease (IBD), either Crohn’s disease or Ulcerative Colitis, are diseases characterized by chronic inflammation of the gastrointestinal tract, disruption of mucosal barrier, gut dysbiosis and vitamin D deficiency. The use of probiotics or vitamin D supplements have been studied individually in different colitis models to determin...

Endometriosis is a gynecological disorder characterized by growth of endometrial tissue outside the uterine cavity, with symptoms which may include chronic pelvic pain and infertility resulting in a decreased quality of life. Previous studies in our laboratory demonstrated that endometriosis animals have increased mesenteric adipose tissue (MAT), i...

Biomedical graduate students receive intensive training in their scientific area of interest yet need additional skills for successful scientific careers. Aim: To promote team building, improve collaborations and enhance communication skills. Methods: An offsite yearly retreat was organized for the graduate students in our NIH-funded RISE graduate...

Introduction We have previously shown that Environmental Enrichment (EE), a multi-modal psychosocial intervention consisting of increased social interaction, novelty, and open spaces, improved disease presentation, anxiety, and immune-related disturbances in the rat model of endometriosis. However, there is a knowledge gap regarding the effects of...

Inflammatory Bowel Diseases (IBD) either Crohn’s disease or Ulcerative colitis are debilitating disorders that affect the gastrointestinal tract with chronic inflammation. Patients with IBD are often characterized by having a change in the gut microbiome composition and decreased levels of vitamin D, which contribute to disease development. Because...

Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue in areas outside the uterus. Previous studies in our laboratory demonstrated that endometriosis animals have increased mesenteric adipose tissue (MAT), inflammation, and implanted endometrial vesicles, which are all decreased by voluntary exercise. Interesti...

Introduction We have previously shown that Environmental Enrichment (EE)-consisting of social support, novelty, and open spaces—decreased disease progression and anxiety in a rat model of endometriosis. We developed a novel EE intervention to be tested in a pilot randomized clinical trial (RCT) in patients with endometriosis, a painful, stressful d...

High-fat diet (HFD) is associated with gut microbiome dysfunction and mental disorders. However, the time-dependence as to when this occurs is unclear. We hypothesized that a short-term HFD causes colonic tissue integrity changes resulting in behavioral changes. Rats were fed HFD or low-fat diet (LFD) for a month and gut microbiome, colon, and beha...

Introduction: Endometriosis is a complex gynecological disorder characterized by the ectopic growth of endometrial tissue. Symptoms of endometriosis are known to impair the quality of life of patients, among these symptoms are dysmenorrhea, chronic pelvic pain, and gastrointestinal (GI) issues. These GI issues are one of the common reasons for mis...

Endometriosis, an estrogen dependent disease, is a gynecological disorder characterized by the growth of endometrial tissue outside the uterine cavity resulting in pain and discomfort. Estrogen plays an important role in the growth and persistence of endometriotic tissue along with inflammation. Estrogen receptor alpha (ERα) expression is significa...

Evidence for beneficial effects of corticotropin releasing hormone (CRH) antagonists in abdominal and pelvic organs is emerging in preclinical studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement a compilation of preclinical studies using CRH receptor antagonists as a treatment for abdominal a...

Introduction Endometriosis is a chronic gynecological disorder characterized by the growth of endometrial glands and stroma outside the endometrial cavity producing inflammation and pain. Previously we demonstrated that modulation of the hypothalamic pituitary adrenal (HPA) axis exacerbates the development and severity of this condition. A physical...

Introduction Monitoring the impact of natural disasters such as pandemics on health and wellbeing is a public health priority. Stress is proven to affect pain intensity and quality of life of endometriosis patients. A cross-sectional study was conducted to determine whether the measures implemented to mitigate COVID-19 infections had a substantial...

Endometriosis is a complex disease characterized by inflammation and the growth of endometrial- like glands and stroma outside the uterine cavity. The pathophysiology of endometriosis is not entirely understood, however, with a prevalence of ~10% of women in their reproductive years, the disease symptoms significantly affect the quality of life of...

We previously demonstrated the negative impact of stress in an animal model of endometriosis. Although its role is unclear, altered levels of vitamin D (VitD) have been found in patients with this condition. VitD signaling through the VitD receptor (VDR) has anti-proliferative properties and induces an anti-inflammatory phenotype in macrophages. We...

There is strong evidence from humans and animal models showing that abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and/or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems, contributing to disease. Stress is known to affect the physiology of pelvic organs and to disturb th...

Endometriosis is a chronic inflammatory condition caused by migration of endometrial tissue outside the uterine cavity resulting in dysmenorrhea, chronic pelvic pain and infertility. Current hormonal or surgical treatments for this debilitating condition are mostly focused towards infertility and pain relief. Physical activity has been shown to mod...

Endometriosis, a gynecological disorder, is characterized by increased levels of the estrogen receptor β (ERβ) in endometrial tissue. Estrogen receptors (ER) are also present in visceral fat and dysregulation of their function is known to correlate with increased white adipose tissue. Preliminary data in our lab found increased mesenteric fat and s...

A physically active lifestyle has been shown to confer preventive health benefits in many chronic conditions, in part by enhancing immunological health. Prolonged moderate exercise increases secretion of IL‐6 that may also promote secretion of the anti‐inflammatory cytokine IL‐10. Endometriosis is a chronic gynecological disorder characterized by p...

Endometriosis is a chronic inflammatory disorder in which endometrial tissue is found outside the uterine cavity. Previous reports suggest that there is a dysregulation of the hypothalamic pituitary adrenal axis during the progression of endometriosis. Our previous report showed that a short-term treatment with antalarmin, a corticotrophin releasin...

Even though HIV-1 replication can be suppressed by combination antiretroviral therapy (cART) inflammatory processes still occur, contributing to comorbidities. Comorbidities are attributed to variety of factors, including HIV-1 mediated inflammation. Several HIV-1 proteins mediate central nervous system (CNS) inflammation, including Nef. Nef is an...

Endometriosis is a painful gynecological disease with no cure and limited therapeutic options. It has been hypothesized that epigenetic drugs can be used as a nonhormonal treatment for endometriosis. This study was conducted to study the efficacy of an inhibitor of the histone methyltransferase EZH2 using an established rat model of endometriosis....

Endometriosis is a gynecological chronic condition caused by endometrial tissue migration outside of the uterine cavity. Some symptoms associated with this inflammatory disease are chronic pelvic pain, infertility and painful menstrual cycles. Physical activity has been shown to promote a healthy lifestyle with beneficial effects on chronic inflamm...

Endometriosis is a chronic gynecological disorder defined as the presence of endometrial glands and stroma outside the endometrial cavity. This condition is characterized by peritoneal inflammation, fibrosis, adhesions and ovarian cysts, which result in chronic pelvic pain, painful periods and infertility. Our previous studies have demonstrated tha...

Physiology Understanding Week (PhUn week) helps to bring science to school students of all levels, exposing them to emerging topics in the area of physiology research. Since 2015, after the NIH Common Fund launched the Molecular Transducers of Physical Activity in Humans research program, topics related to better understanding how exercise impacts...

Graduate students in the biomedical sciences receive intensive training in theory and hands‐on practice related to their scientific area of interest as part of their curriculum. Tools to help them find balance between work and personal life are still needed to ensure a successful graduate experience. We organized a philosophy of science retreat eac...

Endometriosis is a disorder in which the development of uterine‐lining tissue is found outside the uterine cavity causing infertility, pain and stress. Previous studies have shown that stress can negatively affect the progression of the disease. Under the control of the hypothalamic pituitary adrenal (HPA) axis, circulating glucocorticoids regulate...

Introduction Endometriosis is a gynecological disorder in which tissue that normally lines the endometrium grows outside the uterus and commonly results in peritoneal inflammation and infertility. Our previous studies show that stress exacerbates the development of endometriosis symptoms with worsening of colonic damage, and probiotic administratio...

Peripheral inflammation produces an immune response in the brain by the activation of microglia and astrocytes. Astrocytes are also involved in the pain symptoms of chronic diseases such as endometriosis, which is characterized by the growth of uterine tissue outside the reproductive organs. Studies using a mouse model of endometriosis found an inc...

Endometriosis is a disorder in which endometrial tissue is found outside the uterus causing pain, infertility and stress. Finding effective, non-hormonal and long-term treatments for endometriosis still remains one of the most significant challenges in the field. Corticotropin releasing hormone (CRH) is one of the main signaling peptides within the...

Morphological characteristics of endometriosis vesicles illustrated by the stage of estrous cycle at sacrifice. (A) Percent developed vesicles. (B) Group means of the total vesicle weight per rat. (C) Group means for the total vesicle volume per rat. (D) Group means for the total vesicle area per rat. The table illustrates the statistical results o...

Estrous cycle distribution for experiment 1 and experiment 2. (A) The number of rats that were at each stage of the estrous cycle the day of behavioral testing and sacrifice for experiment 1. Estrous cycle before endometriosis surgery was not assessed in these rats. (B) Estrous cycle in rats for experiment 2 was assessed for 10 days prior to induct...

Anxiety behaviors at 7 days after endometriosis induction surgery for experiment 1. Estrous cycle stage at the time of sacrifice was measured by vaginal smear. We did not pre-planned to sacrifice at any particular stage of the cycle but rather at exactly 7 days after the endometriosis induction. (A and B) Total distance traveled in the open field a...

Anxiety behaviors at 60 days after endometriosis induction or sham surgery for experiment 2. Similar to experiment 1, estrous cycle stage at the time of sacrifice was measured by vaginal smear. We did not pre-planned to sacrifice at any particular stage of the cycle but rather at 60 days after the endometriosis induction. (A and B) Total distance t...

According to the Centers for Disease Control and Prevention statistics from 2014, one third of U.S. citizens are obese increasing the risk of other diseases such as metabolic disorders and cardiovascular diseases. Studies have reported that obesity is characterized by inflammation of the intestinal epithelial barrier. One of its components are the...

Introduction Obesity has been associated with a variety of metabolic disorders such as cardiovascular diseases, hyperlipidemia, and diabetes among many others. Also, high fat diet (HFD) is associated with increased inflammation of the intestinal epithelial barrier. The inflammation might cause disruption of the integrity of the tight junctions of t...

Endometriosis is a disorder in which endometrial tissue is found outside the uterus causing pain, infertility and stress. Finding an effective and long-term treatment for endometriosis still remains one of the most significant challenges in the field. Corticotropin releasing hormone (CRH) is one of the main signaling peptides within the hypothalami...

Ceramides are a family of lipids that are present in the cellular membrane. Elevated concentrations of ceramides have been strongly associated with depression in humans. Depression has also been linked to obesity. Since a high‐fat diet increases the chances of obesity, a significant increase in ceramides may be accountable for depression in humans....

Our previous PhUn week activities focused on students from similar grade levels in schools always achieved good learning outcomes. This year due to damaged school facilities after hurricane Maria devastated our island of Puerto Rico, we decided to introduce a Neuroscience theme in a larger combined activity held in a university laboratory environme...

Endometriosis is characterized by endometrial tissue growing in areas outside the reproductive system resulting in discomfort, pain, and infertility. Environmental factors such as stress have been suggested to exacerbate the condition, and our group has previously shown that stress can increase lesion size in a rat model. Animal studies have found...

Obesity has increased during the last couple of decades and is strongly related to cardiovascular disease, hyperlipidemia, diabetes, and neurological disorders, such as depression, which tend to be more prevalent in women. A high fat diet (HFD) is associated with negative effects on the gut microbiome, including increased Firmicutes/Bacteriodetes r...

Treatments for endometriosis include pharmacological or surgical procedures that produce significant side effects. We aimed to determine how environmental enrichment (EE) could impact the progression of endometriosis using the autotransplantation rat model. Female rats were exposed to EE (endo-EE: toys and nesting materials, 4 rats per cage, larger...

Purpose: We have previously shown that stress prior to induction worsens clinical presentation and inflammatory parameters in a rat model of endometriosis. This study was designed to examine whether stress during the development of endometriosis can affect the growth of endometriotic implants through nerve growth and immune alterations. Methods:...

The probiotic mixture VSL#3 attenuates colitis in patients with Inflammatory Bowel Disease (IBD) and in animal models of this condition, but the mechanisms involved are incompletely understood. VSL#3 alters macrophage morphology and secretory profile in vitro in a polarization-dependent manner. We examined the effect of VSL#3 on macrophages in acut...

Purpose: Pain in patients with endometriosis is considered a significant source of stress but does not always correlate with severity of the condition. We have demonstrated that stress can worsen endometriosis in an animal model. Here, we tested the impact of a psychological stress protocol on pain thresholds and pain receptors. Methods: Endomet...

Our review focuses on the colonic macrophage, a monocyte-derived tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as Inflammatory Bowel Disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focu...

Abstract Background: Inflammatory bowel diseases (IBD) are chronic relapsing inflammatory conditions of unknown cause and likely result from the loss of immunological tolerance, which leads to over-activation of the gut immune system. Gut macrophages and dendritic cells (DCs) are essential for maintaining tolerance, but can also contribute to the i...

Studies have examined how endometriosis interacts with the nervous system, but little attention has been paid to opioidergic systems, which are relevant to pain signaling. We used the autotransplantation rat model of endometriosis and allowed to progress for 60 days. The brain was collected and examined for changes in endogenous opioid peptides, mu...

Aim: To determine serum vitamin D levels and colonic vitamin D receptor (VDR) expression in inflammatory bowel disease (IBD) and non-IBD patients and correlate these with histopathology. Methods: Puerto Rican IBD (n = 10) and non-IBD (n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire...

Background: Early life stress has been associated with increasing the risk of developing gastrointestinal disorders by disrupting the brain-gut axis function. Maternal separation (MS) in rats is a well-studied model of early life stress and has been linked to inflammation in adulthood in conditions such as inflammatory bowel disease and irritable b...

Introduction Patients with Inflammatory Bowel Disease are vulnerable to developing extra‐intestinal disorders, usually in the liver and biliary system. Macrophages have been shown to accumulate in the liver in several animal models of colitis. The probiotic mixture VSL#3, which consists of 8 bacterial strains, has been suggested to exert its benefi...

Since 2010, members of the Puerto Rico Physiological Society at PHSU‐PRI have been involved in PhUn week, the annual K‐12 outreach program sponsored by The American Physiological Society. As part of the PhUn week 10th anniversary celebration, graduate students and staff from Ponce Health Sciences University ‐ Ponce Research Institute (PHSU‐PRI) too...

Over the past decade, obesity has become an increasing problem worldwide according to the World Health Organization. Due to increased workload, stress, and other obligations, people tend to eat more often outside the home, frequently picking meals with a higher content of fat, and calories (called “the western diet”) resulting in increased body mas...

Background Early life stress has been associated with increasing the risk of developing gastrointestinal disorders by disrupting the brain‐gut axis function. Maternal separation (MS) in rats is a well‐studied model of early life stress and has been linked to inflammation in adulthood in conditions such as inflammatory bowel disease and irritable bo...

Although the role of vitamin D in endometriosis is still unclear, vitamin D signaling through the vitamin D receptor (VDR) is associated with anti‐proliferative and anti‐inflammatory effects. We previously reported differential VDR expression in our endometriosis model when the animals were exposed to stress. Vitamin D can induce an anti‐inflammato...

Background Our previous work has shown that the probiotic mixture VSL#3 alters the morphology and secretory profile of proinflammatory (M1), anti‐inflammatory (M2), and unpolarized macrophages in vitro. The effect of VSL#3 on macrophages in vivo is unclear. This knowledge may prove useful for developing and improving treatments for colitis in patie...

High fat diet consumption is associated with a variety of metabolic disorders such as diabetes, hyperlipidemia, and cardiovascular diseases among others. Also, an intake of high fat is associated with inflammation of the intestinal epithelial barrier, and characterized by increased intestinal permeability. This increased permeability is characteriz...

Background: Symptoms of endometriosis, such as pain and infertility, are considered significant sources of stress. In many chronic conditions, exercise can act as a stress buffer and influence pain perception. We tested the impact of swimming exercise on pain perception and pain receptors in an animal model of endometriosis. Methods: Endometrios...

The conventional approach of double immunostaining to visualize more than one protein in tissues or cells using antibodies from two different host species is not always feasible due to limitations with antibody availability. Previously reported methodologies for performing multiple immunostains on the same tissue or cells with antibodies originatin...

The use and validity of the Graduate Record Examination General Test (GRE) to predict the success of graduate school applicants is heavily debated, especially for its possible impact on the selection of underrepresented minorities into science, technology, engineering, and math fields. To better identify candidates who would succeed in our program...

Puerto Rico Physiological Society has been conducting PhUn Week activities in schools located in the south of the Island. This year junior students received talks and participated in hands‐on activities related to several topics in physiology. Aim The main was to provide information on basic physiological concepts, what scientists do, and how to p...

To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sp...

Barriers persist in the development and delivery of effective cancer therapies to under-represented minority populations. In Puerto Rico, cancer is the second leading cause of death, yet cancer research awareness and training opportunities remain somewhat limited on the island. These limitations hinder progress toward decreasing the cancer health d...

We have previously shown detrimental effects of stress in an animal model of endometriosis. We now investigated whether the ability to control stress can affect disease parameters. Endometriosis was surgically induced in female Sprague-Dawley rats before exposing animals to a controllable (submerged platform) or uncontrollable (no platform) swim st...

Background: Patients with Inflammatory Bowel Disease (IBD), most commonly Crohn's disease (CD) or ulcerative colitis (UC), suffer from chronic intestinal inflammation of unknown etiology. Increased proinflammatory macrophages (M1) have been documented in tissue from patients with CD. Anti-inflammatory macrophages (M2) may play a role in UC given t...

Recently, epigenetic factors, including histone modifications, and environmental factors have shown to play an active role in endometriosis. We have recently shown that the levels of histone de‐acetylates (HDACs) are higher and that histone acetylation marks are decreased in endometriosis lesions. Also, stress contribute to the development of highe...

Background: Endometriosis is characterized by the growth of endometrial tissue in areas such as the peritoneal cavity and colon causing pain and discomfort. We have previously demonstrated that rats with explants of endometrial tissue in the peritoneal cavity subjected to stress showed a significant increase in the size of endometrial lesions. Chem...

Endometriosis is characterized by peritoneal inflammation, infertility and chronic pelvic pain that substantially affect quality of life. Since stress can affect the immune system and recruitment of inflammatory cells it may contribute to this condition. Vitamin D receptor (VDR) is associated with anti‐proliferative and anti‐inflammatory properties...

Gastrointestinal (GI) pathology is a recurrent problem during HIV infection and progression. HIV enteropathy may be associated with a specific cause; however some HIV‐positive individuals present idiopathic enteropathy that appears to involve inflammatory processes. The presence of increased plasma LPS due to GI inflammation in patients with HIV as...

Individual basic criteria (eg. GRE, GPA) commonly used by graduate school admissions committees are often not suitable predictors for success at our institution, possibly due to differences in language and culture. Therefore we developed a composite score (CS) which uses evidence‐based predictors of success to evaluate our incoming applicants to be...

Endometriosis is a debilitating disease characterized by pelvic pain, dysmenorrhea and dyspareunia. These symptoms produce stress on the individual and impact daily life activities. It is still poorly understood how stress affects endometriosis associated pain. We aimed to measure levels of the endogenous opioid peptide enkephalin (ENK) in the peri...

Students pursuing graduate degrees in the biomedical sciences require specific laboratory skills. We designed a course to teach these skills, ensuring uniformity and faster adaption in their education. Aim To test whether the course improved the technical ability and theoretical knowledge of first‐year graduate students. Methods The experiments w...

BACKGROUND Previous studies have implicated NK‐1R, Cox‐2, pEGFR, and VDR in the development of sporadic dysplasia and colorectal cancer (CRC). The role of these proteins in CAC remains unclear. AIM Determine the expression of NK‐1R, Cox‐2, pEGFR, and VDR in tissue from patients with CAC. METHODS Tissue samples from 6 patients with CAC were staine...